Comparative assessment of the sensory irritation potency in mice and rats nose-only exposed to ammonia in dry and humidified atmospheres

Young adult male Wistar rats, a species commonly used in inhalation toxicity studies, and OF1 mice, a species often used in sensory irritation studies, were simultaneously nose-only exposed for 45-min to ammonia in concentrations from 92 to 1243 mg/m3. This study examined airway reflexes by the changes in respiratory patterns elicited by ammonia in either dry, steam-humidified (approximately 95% relative humidity) or aqueous aerosol containing atmospheres. This served the objective to explore whether high concentrations of anhydrous ammonia and/or high humidity and aqueous aerosol change the predominant nasal deposition site to more distal locations in the lung. Animals from all groups tolerated the exposure without evidence of respiratory tract irritation, changes in body and lung weights. The evoked changes on breathing patterns resembled those known to occur following exposure to ‘upper respiratory tract sensory irritants’, rapid in onset and reversibility. Reflex stimulation from the lower airways was not observed in any group. While mice showed some adaption during the 45-min exposure period, rats displayed more stable changes in respiratory patterns. In this species humidity- or aqueous aerosol-related changes in sensory irritation potency did not occur to any appreciable extent. The respiratory decrease 50%, RD50, was 972 and 905 mg/m3 in dry and wet air, respectively. In contrast, mice appeared to more susceptible to ammonia in presence of dry air (the RD50, was 582 and 732 mg/m3 in dry and wet air, respectively). In summary, it was shown that the sensory irritation potency of ammonia does not increase when inhaling wet atmospheres nor penetrates this gas into the lower airways up to 1243 mg/m3 × 45-min. The mild-to-moderate sensory irritation-related effects observed at ≈400 mg/m3 (571 ppm) × 45-min do not appear to be offensive enough to impair escape as a result of upper airway sensations. Interestingly, this rat-based estimate matches almost exactly the experienced-based RAM TRAC recommendations of 696 and 492 ppm for 30 and 60 min, respectively.